P1315: THE CHRONOLOGICAL SEQUENCE OF 12 GY TOTAL BODY IRRADIATION AND CYCLOPHOSPHAMIDE CONDITIONING DOES NOT IMPACT OUTCOMES IN AML PATIENTS UNDERGOING MYELOABLATIVE ALLOGENEIC STEM CELL TRANSPLANTATION
Authors: Georg-Nikolaus Franke, Jule Ussmann, Donata Backhaus, Nils Henrik Nicolay, Vladan Vucinic, Marco Herling, Birthe Schetschorke, Saskia Hell, Uwe Platzbecker, Sebastian Schwind, Madlen Jentzsch
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Allogeneic hematopoietic stem cell transplantion (allo-HSCT) is considered standard of care in eligible patients (pts) with acute myeloid leukemia (AML) and intermediate or adverse risk in 1st complete remission (CR) as well as in pts suffering relapse. Myeloablative conditioning with cyclophosphamide (Cy) and 12 Gy total body irradiation (TBI) is often used in younger pts with high-risk features. Different modes of TBI (dose intensity, single vs fractioned doses, rate of delivery) have been compared in the past but, to our knowledge, no formal comparison of the optimal schedule of TBI in relation to chemotherapy in this setting has been published. Aims: To compare outcomes of pts with AML transplanted from an allogeneic donor after conditioning with either Cy followed by TBI or TBI prior to Cy. Methods: We retrospectively analyzed 144 pts with AML receiving an allo-HSCT with either Cy on day -5 and -4 followed by 12Gy TBI from day -3 to -1 (n=90) or TBI from day -6 to -4 followed by Cy on day -3 and -2 (n=56) before allo-HSCT between 2001 and 2018. Median age at the time of allo-HSCT was 42.5 years (y, range 14.8 – 57.6 y) and the median follow up after allo-HSCT was 4.5 y. 55 pts had a matched sibling donor, 78 a matched unrelated donor (URD) and 11 a mismatched URD. 127 pts were in CR at the time of HSCT, 14 pts had a CR with incomplete recovery (CRi), and 3 pts had more advanced disease. European LeukemiaNet 2022 (ELN22) risk classification was available for 101 pts (favorable/intermediate/adverse: 34%/31%/35%). Results: Pts receiving the CyTBI sequence less often had a complex karyotype (CKT, P=.02), and more often a FTL3-TKD mutation (P=.02). There were no other significantly distinct clinical, genetic, or HSCT-related characteristics between both groups. For the whole pts cohort, 5-y-overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) was 69%, 33%, and 11%, respectively. Comparing both sequences, there was a trend for shorter CIR (P=.09, at 5y, CyTBI 39% vs TBICy 24%, Figure 1A) but no significantly different NRM (P=.98, at 5y, CyTBI 10% vs TBICy 11%) or OS (P=.20, at 5y, CyTBI 66% vs TBICy 74%, Figure 1B) between pts receiving CyTBI or TBICy. When we excluded pts with a CKT from outcome analyses, CIR (P=.20, Figure 1C), NRM (P=.77) and OS (P=.30) were similar between pts receiving CyTBI and TBICy. Similarly, in separate analyses in ELN22 favorable (CIR P=.40, NRM P=.73, OS P>.99), intermediate (CIR P=.10, NRM P=.55, OS P=.90), and adverse risk pts (CIR P=.93, NRM P=.59, OS P=.10), no distinct outcomes were observed. Also in multivariate analyses, the sequence of Cy and TBI did not impact CIR (significant variables were ELN22 risk [HR 2.44, 95% CI 1.66-3.56, P<.001] and CR/CRi at HSCT [HR 0.09, 95% CI 0.04-0.24, P<.001]) or OS (significant variables were ELN22 [HR 2.09, 95% CI 1.29-3.38, P=.003], CR/CRi at HSCT [HR 0.13, 95% CI 0.03-0.50], P=.003, and Age >40 y at allo-HSCT [HR 2.50, 95% CI 1.30-6.70, P=.01]). Neither the time to leukocyte (median 15 days vs 14 days, P=.62) or platelet engraftment (median 13 days vs 13 days, P=.25) nor the incidences of ≥ grade 2 acute (20% vs 25%, P=.50) or chronic Graft-vs-Host-Disease (GvHD, 45% vs 43%, P=.84) after allo-HSCT differed between pts receiving CyTBI or TBICy, respectively. Summary/Conclusion: In our cohort, no impact of the sequence of TBI and Cy on hematologic recovery, rates of acute or chronic GvHD, CIR, NRM, or OS was shown. In conclusion, TBI can be scheduled from day -6 to -4 or day -3 to -1 before HSCT as necessary for optimal timing of the allo-HSCT without impact on patients’ outcome.Keywords: Acute myeloid leukemia, Conditioning, Total body irradiation